Background <p>This research aimed to estimate the prognostic value of the platelet-to-lymphocyte ratio (PLR) in colorectal cancer (CRC) patients receiving chemotherapy.</p> Methods <p>Embase, the Cochrane Library, Web of Science, and PubMed were searched from inception to March 20, 2025. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to appraise the predictive significance of PLR among CRC patients receiving chemotherapy. The robustness of the findings and potential publication bias were assessed by sensitivity analysis and Egger’s test, respectively. The impact of confounding variables was investigated through subgroup and regression analyses.</p> Results <p>In total, 33 studies involving 7,529 individuals were included. Statistical analysis of categorical variables demonstrated that an increased PLR was significantly related to overall survival (OS) (HR = 1.33, 95% CI = 1.14–1.54), progression-free survival (PFS) (HR = 1.32, 95% CI = 1.06–1.63), and relapse-free survival (RFS) (HR = 1.77, 95% CI = 1.13–2.77) in CRC patients receiving chemotherapy, whereas no significant relationship was found with disease-free survival (DFS) (HR = 1.19, 95% CI = 0.84–1.69). Subgroup analyses indicated that, among metastatic CRC patients, a higher PLR was significantly linked to unfavorable OS and DFS. In CRC patients receiving adjuvant chemotherapy or chemotherapy with or without targeted therapy, high PLR was significantly related to worse OS and PFS.</p> Conclusion <p>An elevated PLR is related to adverse prognosis among CRC patients undergoing chemotherapy. In clinical practice, PLR may be a promising and cost-effective predictive marker for this population.</p>